Murine delayed-type hypersensitivity granuloma: an improved model for the identification and evaluation of different classes of anti-arthritic drugs.
The present study examined the effects of five different classes of anti-inflammatory/immunoregulatory drugs using a mouse model of mBSA-induced delayed-type hypersensitivity granuloma (DTH GRA) to measure immune-mediated chronic inflammatory tissue formation. The compounds were administered orally daily following induction of DTH GRA (days 0 to 4); granulomata were quantitated gravimetrically on day 5. NSAIDs, with the exception of flurbiprofen, showed little activity in comparison with the steroids dexamethasone (1-3 mg/kg/day, orally) and prednisolone (3-10 mg/kg/day, orally), which caused significant suppression of DTH GRA tissue (65-76% and 26-68%, respectively). The "immunoregulatory" compounds levamisole and D(-)penicillamine were inactive, whereas cyclophosphamide (5-50 mg/kg/day, orally) reduced the response by 24-83%. The "interferon alpha-inducers" Tilorone, U-54,461, and U-56,499 were also potent inhibitors of the DTH GRA response; U-54,462, a weak interferon alpha-inducer, was inactive. Cyclosporin A (50-100 mg/kg/day, orally) suppressed DTH GRA most effectively when administered on days 3 and 4 (66% and 97%) of the five-day granuloma response (treatment was ineffective when given on days 1 and 2). We conclude that the DTH GRA response described above may be useful for evaluating different types of unique therapeutic agents that are effective in the treatment of chronic immuno-inflammatory disease such as rheumatoid arthritis.
Dunn
C J
CJ
Department of Hypersensitivity Disease Research, Upjohn Company, Kalamazoo, Michigan 49001.
Galinet
L A
LA
Gibbons
A J
AJ
Shields
S K
SK
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006099:Granuloma / Q000188:drug therapy* / Q000209:etiology; D006968:Hypersensitivity, Delayed; D007369:Interferon Inducers / Q000627:therapeutic use; D051379:Mice
D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005938:Glucocorticoids; D007369:Interferon Inducers